1. Field of the Invention
The invention relates to a novel process for preparation of 4-acetyl-2-substituted-imidazoles and intermediate 2-chloro-1-alkylthio-1-butene-3-one and 2-chloro-1,1-dialkoxy-3-butanones.
2. Description of the Prior Art
Methods for preparation of 4-acetyl-2-alkyl (or aralkyl)imidazoles and their utility as intermediates for preparation of 2-guanidino-4-imidazolylthiazole compounds, useful as antisecretory agents for treatment of peptic ulcers and other conditions caused or aggravated by gastric hyperacidity, are disclosed in U.S. Pat. No. 4,374,843, issued Feb. 22, 1983. These methods comprise irradiation of 1-acetyl-2-substituted imidazoles with ultraviolet light and reaction of a 2-halo-1-n-alkoxy-1-buten-3-one, e.g. ##STR4## with an amidine or a salt thereof, in the presence of reaction inert solvent and base. The yields of 4-acetyl-2-methylimidazole by these two processes are low, on the order of 40-50 and 20-30%, respectively.
In copending application Ser. No. 445,787, filed Dec. 1, 1982, assigned to the same assignee, a process is disclosed for making 4-acetyl-2-methyl-imidazole (I, R.dbd.CH.sub.3) from 2-methylimidazole-4-carboxaldehyde, in which the 1-position is protected e.g. by a benzyl group, by reaction with a methylmagnesium halide, e.g., methylmagnesium chloride, followed by deblocking and oxidation, or by oxidation, then deblocking.
The reaction of chloroacetyl chloride and aluminum chloride with a molar excess of 1,2-dichloroethylene has been reported by Catch et al., J. Chem. Soc. (London) 278 (1948) to afford chloromethyl 1,2,2-trichloroethyl ketone. McLamore et al., J. Org. Chem., 20, 109 (1955) have reported propionyl chloride to react with 1,2-dichloroethylene to provide ethyl 1,2,2-trichloroethyl ketone.
Methyl 1,2-dichlorovinyl ketone (IV) has been prepared by a three-step synthesis from 1,2-dichloro-1,3-butadiene by Petrov, J. Gen. Chem. (U.S.S.R.) 13, 230 (1943); Chem. Abstr., 38, 1467.sup.4 (1944).